Common Genotypic Polymorphisms in Glutathione S-Transferases in Mild and Severe Falciparum Malaria in Tanzanian Children

Reginald A. Kavishe Departments of Pharmacology and Toxicology, Medical Microbiology, Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Kilimanjaro Christian Medical College of Tumaini University, Tanzania

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Teun Bousema Departments of Pharmacology and Toxicology, Medical Microbiology, Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Kilimanjaro Christian Medical College of Tumaini University, Tanzania

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Seif A. Shekalaghe Departments of Pharmacology and Toxicology, Medical Microbiology, Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Kilimanjaro Christian Medical College of Tumaini University, Tanzania

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Robert W. Sauerwein Departments of Pharmacology and Toxicology, Medical Microbiology, Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Kilimanjaro Christian Medical College of Tumaini University, Tanzania

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Frank W. Mosha Departments of Pharmacology and Toxicology, Medical Microbiology, Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Kilimanjaro Christian Medical College of Tumaini University, Tanzania

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Andre J. A. M. van der Ven Departments of Pharmacology and Toxicology, Medical Microbiology, Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Kilimanjaro Christian Medical College of Tumaini University, Tanzania

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Frans G. M. Russel Departments of Pharmacology and Toxicology, Medical Microbiology, Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Kilimanjaro Christian Medical College of Tumaini University, Tanzania

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Jan B. Koenderink Departments of Pharmacology and Toxicology, Medical Microbiology, Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Kilimanjaro Christian Medical College of Tumaini University, Tanzania

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Malaria infection induces oxidative stress in the host cells. Antioxidant enzymes such as glutathione S-transferases (GSTs) are responsible for fighting reactive oxygen species and reduction of oxidative stress. Common GST polymorphisms have been associated with susceptibility to different diseases whose pathologies involve oxidative stress. In this study, we tested the hypothesis that GST polymorphisms that lead to reduced or lack of enzyme activity are associated with severe Plasmodium falciparum malarial anemia. We studied the genotypic distribution of GSTM1, GSTT1, and GSTP1 polymorphisms between mild malaria (N = 107) and severe malarial anemia (N = 50) in Tanzanian children. We did not find a significant relationship with the GSTT1 polymorphism. GSTM1-null was higher in the severe malaria anemia group but the difference was not significant (P = 0.08). However, a significant association of GSTP1 I105V genotype with severe malarial anemia was discovered (26.0% against 10.3% mild malaria, P = 0.004). We concluded that GSTP1 and possibly GSTM1 may protect against severe falciparum malaria in children.

Author Notes

  • 1

    Pagola S, Stephens PW, Bohle DS, Kosar AD, Madsen SK, 2000. The structure of malaria pigment beta-haematin. Nature 404 :307–310.

  • 2

    Slater AF, 1993. Chloroquine: mechanism of drug action and resistance in Plasmodium falciparum. Pharmacol Ther 57 :203–235.

  • 3

    Pandey AV, Bisht H, Babbarwal VK, Srivastava J, Pandey KC, Chauhan VS, 2001. Mechanism of malarial haem detoxification inhibition by chloroquine. Biochem J 355 :333–338.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Maitland K, Marsh K, 2004. Pathophysiology of severe malaria in children. Acta Trop 90 :131–140.

  • 5

    Schwarzer E, Turrini F, Giribaldi G, Cappadoro M, Arese P, 1993. Phagocytosis of P. falciparum malarial pigment hemozoin by human monocytes inactivates monocyte protein kinase C. Biochim Biophys Acta 1181 :51–54.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Schwarzer E, Arese P, 1996. Phagocytosis of malarial pigment hemozoin inhibits NADPH-oxidase activity in human monocyte-derived macrophages. Biochim Biophys Acta 1316 :169–175.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Taramelli D, Basilico N, Pagani E, Grande R, Monti D, Ghione M, Olliaro P, 1995. The heme moiety of malaria pigment (beta-hematin) mediates the inhibition of nitric oxide and tumor necrosis factor-alpha production by lipopolysaccharide-stimulated macrophages. Exp Parasitol 81 :501–511.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Becker K, Tilley L, Vennerstrom JL, Roberts D, Rogerson S, Ginsburg H, 2004. Oxidative stress in malaria parasite-infected erythrocytes: host-parasite interactions. Int J Parasitol 34 :163–189.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Ali-Osman F, Akande O, Antoun G, Mao JX, Buolamwini J, 1997. Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. Evidence for differential catalytic activity of the encoded proteins. J Biol Chem 272 :10004–10012.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Strange RC, Jones PW, Fryer AA, 2000. Glutathione S-transferase: genetics and role in toxicology. Toxicol Lett 112–113 :357–363.

  • 11

    Strange RC, Lear JT, Fryer AA, 1998. Glutathione S-transferase polymorphisms: influence on susceptibility to cancer. Chem Biol Interact 111–112 :351–364.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Kavishe RA, Koenderink JB, McCall MB, Peters WH, Mulder B, Hermsen CC, Sauerwine RW, Russel FG, Van der Ven AJ, 2006. Short report: severe Plasmodium falciparum malaria in Cameroon: associated with the glutathione S-transferase M1 null genotype. Am J Trop Med Hyg 75 :827–829.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Shekalaghe S, Drakeley C, Gosling R, Ndaro A, van Meegeren M, Enevold A, Alifrangis M, Mosha F, Sauerwine R, Bousema T, 2007. Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine-pyrimethamine and artesunate. PLoS Clin Trials 2 :e1023.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Marsh K, Forster D, Waruiru C, Mwangi I, Winstanley M, Marsh V, Newton C, Winstanley P, Peshu N, et al., 1995. Indicators of life-threatening malaria in African children. N Engl J Med 332 :1399–1404.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Molyneux ME, Taylor TE, Wirima JJ, Borgstein A, 1989. Clinical features and prognostic indicators in pediatric cerebral malaria: a study of 131 comatose Malawian children. Q J Med 71 :441–459.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Pemble S, Schroeder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM, et al., 1994. Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 300 :271–276.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Bröckmoller J, Kerb R, Drakoulis N, Nitz M, Roors I, 1993. Genotype and phenotype of glutathione S-transferase class isoenzymes and psi in lung cancer patients and controls. Lung Cancer 10 :273.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Watson MA, Stewart RK, Smith GBJ, Massey TE, Bell DA, 1998. Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis 19 :275–280.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Mcglynn KA, Rosvold EA, Lustbader ED, Hu Y, Clapper ML, Zhou TL, et al., 1995. Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B-1. Proc Natl Acad Sci USA 92 :2384–2387.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Mukanganyama S, Masimirembwa CM, Naik YS, Hasler JA, 1997. Phenotyping of the glutathione S-transferase M1 polymorphism in Zimbabweans and the effects of chloroquine on blood glutathione S-transferases M1 and A. Clin Chim Acta 265 :145–155.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Rossini A, Rapozo DC, Amorim LM, Macedo JM, Medina R, Neto JF, Gallo CV, Pinto LF, 2002. Frequencies of GSTM1, GSTT1, and GSTP1 polymorphisms in a Brazilian population. Genet Mol Res 1 :233–240.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Tiemersma EW, Omer RE, Bunschoten A, van’t Veer P, Kok FJ, Idris MO, Kadaru AM, Fedail SS, Kampman E, 2001. Role of genetic polymorphism of glutathione-S-transferase T1 and microsomal epoxide hydrolase in aflatoxin-associated hepatocellular carcinoma. Cancer Epidemiol Biomarkers Prev 10 :785–791.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Zhao L, Alldersea J, Fryer A, Tighe A, Ollier B, Thomson W, Jones P, Strange R, 1994. Polymorphism at the glutathione S-transferase GSTM1 locus: a study of the frequencies of the GSTM1-A, B, A/B and null phenotypes in Nigerians. Clin Chim Acta 225 :85–88.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Schneider J, Bernges U, Philipp M, Woitowitz HJ, 2004. GSTM1, GSTT1, and GSTP1 polymorphism and lung cancer risk in relation to tobacco smoking. Cancer Lett 208 :65–74.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Hu X, Xia H, Srivastava SK, Herzog C, Awasthi YC, Ji XH, Zimniak P, Singh SV, 1997. Activity of four allelic forms of glutathione S-transferase hGSTP1-1 for diol epoxides of polycyclic aromatic hydrocarbons. Biochem Biophys Res Commun 238 :397–402.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Sundberg K, Johansson AS, Stenberg G, Widersten M, Seidel A, Mannervik B, Jernström B, 1998. Differences in the catalytic efficiencies of allelic variants of glutathione transferase P1-1 towards carcinogenic diol epoxides of polycyclic aromatic hydrocarbons. Carcinogenesis 19 :433–436.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Wang LH, Groves MJ, Hepburn MD, Bowen DT, 2000. Glutathione S-transferase enzyme expression in hematopoietic cell lines implies a differential protective role for T1 and A1 isoenzymes in erythroid and for M1 in lymphoid lineages. Haematologica 85 :573–579.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Famin O, Krugliak M, Ginsburg H, 1999. Kinetics of inhibition of glutathione-mediated degradation of ferriprotoporphyrin IX by antimalarial drugs. Biochem Pharmacol 58 :59–68.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Ginsburg H, Famin O, Zhang JM, Krugliak M, 1998. Inhibition of glutathione-dependent degradation of heme by chloroquine and amodiaquine as a possible basis for their antimalarial mode of action. Biochem Pharmacol 56 :1305–1313.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Deharo E, Barkan D, Krugliak M, Golenser J, Ginsburg H, 2003. Potentiation of the antimalarial action of chloroquine in rodent malaria by drugs known to reduce cellular glutathione levels. Biochem Pharmacol 66 :809–817.

    • PubMed
    • Search Google Scholar
    • Export Citation
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